The goal of this research is to understand how the transcriptional regulatory protein 4 encoded by herpes simplex virus (HSV) interacts with the infected cell nucleus to alter transcription of the viral genome. We propose experiments to determine the host and viral proteins with which protein 4 interacts in the cytoplasm during transport into the nucleus. We also propose to investigate the interaction of this protein with host and viral proteins and host and viral DNA in the cell nucleus. In this way we will determine the maturational pathway of the protein in molecular terms. We will also investigate the changes in the molecular interactions of the protein encoded by temperature-sensitive mutants. We will attempt to determine the changes in molecular interactions that occur when the transcriptional regulatory function of protein 4 is inactivated. This may yield information about the mechanism by which this protein regulates transcription. This viral gene function may be important in the regulation of viral replication during the establishment or maintenance of latent infection. Protein 4 has been reported to be expressed in latently infected ganglia. Thus, an understanding of how this protein regulates viral gene expression may yield information about the mechanism by which HSV establishes a latent infection.